Sheldon Crane reported an explosion when using magnesium nitride to convert esters to amides through a protocol similar to that reported in our recent publication (C&EN, April 13, page 2; Org. Lett.2008,10, 3623). Our other published procedures for the preparation of dihydropyridines (Org. Lett.2008, 10, 3627) and pyrroles (Synlett.2008, 17, 2597) have all proceeded without incident over a large number of experiments.

Although our procedure was not followed exactly and the scale of the reaction was tripled, we were extremely concerned that an accident had resulted. Without knowing the root cause of the explosion, whether it is inherent to the reaction, or due to faulty glassware or contamination of the magnesium nitride (possibly with magnesium azide), or due to the water content of the methanol, we reinvestigated our procedure with different substrates and fresh samples.

Despite having carried out more than 200 magnesium nitride reactions in the past without incident, we also observed explosions when heterocyclic (furan and indole) esters were used as substrates and while following our precise experimental conditions as reported in the supporting information in the initial Organic Letters paper. In view of these results, we must recommend that the procedure be followed only with extreme caution.

We are currently investigating modified experimental procedures to determine whether safer ways of carrying out these reactions can be found. These investigations will center on limiting the scale of the reaction (less than 0.25 mmol) and placing the reaction vessel in an ice-bath for approximately one hour to mitigate any initial exotherm before heating slowly to 80 ºC.

Although not wishing to be bound by any theory, we believe that the explosions were caused by an initial exothermic ammonia-generating reaction and a following or simultaneous runaway reaction between the highly concentrated ammonia and ester substrate.